Knowledge management for systems biology a general and visually driven framework applied to translational medicine

Background: To enhance our understanding of complex biological systems like diseases we need to put all of the available data into context and use this to detect relations, pattern and rules which allow predictive hypotheses to be defined. Life science has become a data rich science with information about the behaviour of millions of entities like genes, chemical compounds, diseases, cell types and organs, which are organised in many different databases and/or spread throughout the literature. Existing knowledge such as genotype - phenotype relations or signal transduction pathways must be semantically integrated and dynamically organised into structured networks that are connected with clinical and experimental data. Different approaches to this challenge exist but so far none has proven entirely satisfactory. Results: To address this challenge we previously developed a generic knowledge management framework, BioXM™, which allows the dynamic, graphic generation of domain specific knowledge representation models based on specific objects and their relations supporting annotations and ontologies. Here we demonstrate the utility of BioXM for knowledge management in systems biology as part of the EU FP6 BioBridge project on translational approaches to chronic diseases. From clinical and experimental data, text-mining results and public databases we generate a chronic obstructive pulmonary disease (COPD) knowledge base and demonstrate its use by mining specific molecular networks together with integrated clinical and experimental data. Conclusions: We generate the first semantically integrated COPD specific public knowledge base and find that for the integration of clinical and experimental data with pre-existing knowledge the configuration based set-up enabled by BioXM reduced implementation time and effort for the knowledge base compared to similar systems implemented as classical software development projects. The knowledgebase enables the retrieval of sub-networks including protein-protein interaction, pathway, gene - disease and gene - compound data which are used for subsequent data analysis, modelling and simulation. Pre-structured queries and reports enhance usability; establishing their use in everyday clinical settings requires further simplification with a browser based interface which is currently under development.

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Contient : 1 Recueil de généalogies portugaises ; 2 Recueil de généalogies extraites "de hum livro de Nunalvares Pereira" ; 3 Recueil de généalogies : "Estos linages que se siguen se copiaron de un libro de Alonsso Lopez de Haro de los linages de Portugal, y, por lo que dize en el de los Pimenteles, parece se le dio Nunalbarez Pereyra." ; 4 "Desçendencia dos Teives feita por D. Belchor de Teive." ; 5 Notes sur divers membres de la famille de Mello ou Merlo ; 6 "Familia y quadrilla de Blasco Ximeno." Cette généalogie se termine par une notice sur D. Gomez d'Avila y Toledo, deuxième marquis de Velada ; 7 "Linhagem dos de Castelbranco, recopilada por Dom Manoel de Castelbranco, conde de Villanova." ; 8 Notes généalogiques sur les familles Pinheiro, Manoel et Tserclaes ; 9 "Memoria dos titulos que os reis de Portugal criarão de novo neste reyno," de João Ier à Philippe III ; 10 "Los grandes y titulos de Castilla." ; 11 "Visoreys e governadores da India." ; 12 Notes généalogiques sur les Souza et les Maldonado ; 13 "Adiantados que ouve em Portugal." ; 14 "Epitaphios que estão no mosteiro de S. Antonio da Castanheyra." ; 15-34 Documents relatifs à la prise de la ville de Salvador (Bahia, Brésil) par les hollandais (1624) et à la reprise par l'armée hispano-portugaise (1625) ; 15 "Lista dos navios, capitaes d'elles e soldados, fidalgos e nobres que se embarcarão e partirão ao soccorro da Bahia, a 21 de novembro de 1624, sendo capitão geral d'esta armada don Manoel de Meneses." ; 16 "Relaçaõ do dinheiro e cousas reduzidas a elle com que este reyno servio a Sua Magd na ocasiaõ do apresto da armada para o socorro da Bahia no Brasil, que vae ao todo noventa e tres contos coatrocentos e hum mil." 1624 ; 17 "Relaçaõ da armada que partio de Lisbóa em socorro da Bahia e do susseço que teve." ; 18 "Carta para hum fidalgo recidente na corte de Madrid, em que brevemente se relata o corpo principal de toda a armada, que d'este porto de Lixboa salio para a empreza da Bahya, aos 23 de novembro de 1624." Lisbonne, 12 décembre 1624 ; 19 "Relaçaõ das armadas de Sua Magde do dia em que chegaraõ a Bahia e do que se tem feito na expugnaçaõ do enemigo, desde 29 de março que foi vespera de Pascoa, em que deraõ fundo na dita Baia as armadas, ate 22 abril, em que se mandou a Pernambuco o papel de que se tirou esta rellaçaõ, a qual mandaraõ os governadores de Portugal a Sua Magde." 1625 ; 20 "Relaçion de Lorenço Perez Carballo de lo que pasa en la Baya, de quinçe de abril de 1625." ; 21 "Copia da carta que dom Manoel de Menezes, capitaõ mor da armada da esquadra de Portugal, escreveo a S. Mgde, da Bahia, dando conta do que succedeo nella, desde 29 de março te 12 de mayo de 1625." ; 22 "Relaçaõ de que o capitaõ don Manoel de Meneses faz mençaõ na sua carta atraz." 1625 ; 23 "Discurso breve del suçeso que han tenido las armas de su Magd en la jornada del Brasil, desde que salieron de España asta la rrestauraçion de la çiudad de San Salvador, que tomaron los Olandeses en diez de mayo del año pasado de mill y seisçientos y veinte y quatro... Fecha en diez de mayo de mill y seisçientos y veinte y cinco." ; 24 "Copia de las cartas y respuestas que ubo de parte de los Olandeses y Don Fadrique de Toledo Ossorio, desde 28 de abril [1625] hasta 30 que se rindio la plaza" de San Salvador ; 25 "Capitulos conspirados por el sor Coronel y los del Conssejo en la Baya para ofreçer a su Exa Don Fadrique de Toledo, general por su Mgd d'España." 29 et 30 avril 1625 ; 26" Relacion del viaje y sucesso de la Armada que por mandado de su Magestad partio al Brasil, a echar de alli los enemigos que lo ocupavam. Francisco de Avendaño y Vilela. En Sevilla por Francisco de Lyra, año de 1625." ; 27 "Relaçion de la jornada que ba haziendo la armada real a las partes del Brasil, que salio de la baya de Cadiz, martes á catorze de henero de seiscientos y veinte y cinco." ; 28 État-major des tercios de D. Juan de Orellana et D. Pedro Osorio et du tercio de Naples du marquis de Torrecusso, embarqués à Cadix pour le Brésil, le 14 janvier 1625 ; 29 "Brevis, succinta ac vera narratio expeditionis illius, quam quidam mercatores sub auspiciis et autoritate illustrium D. D. ordinum Holandiae, Zelandiae, etc. suseperunt in Brasilium, anno 1623." ; 30 Relation de combats entre Portugais et Hollandais sur les côtes du Brésil ; 31 Notes généalogiques sur les familles Costa, Correa de Moura et Moreno, communiquées au compilateur du recueil par D. Luis Lobo et D. Antonio Correa Barem ; 32 "Relaçaõ do que o capitaõ Francisco de Padilha fes en quanto andou nos asaltos ate a vinda da armada." 1624 ; 33 Relation de l'attaque de Sam Bento au Brésil, en 1625 ; 34 Relation de l'expédition des flottes espagnole et portugaise au Brésil et de la prise de San Salvador. 1625

A general definition and nomenclature for alternative splicing events

Understanding the molecular mechanisms responsible for the regulation of the transcriptome present in eukaryotic cells isone of the most challenging tasks in the postgenomic era. In this regard, alternative splicing (AS) is a key phenomenoncontributing to the production of different mature transcripts from the same primary RNA sequence. As a plethora ofdifferent transcript forms is available in databases, a first step to uncover the biology that drives AS is to identify thedifferent types of reflected splicing variation. In this work, we present a general definition of the AS event along with anotation system that involves the relative positions of the splice sites. This nomenclature univocally and dynamically assignsa specific ‘‘AS code’’ to every possible pattern of splicing variation. On the basis of this definition and the correspondingcodes, we have developed a computational tool (AStalavista) that automatically characterizes the complete landscape of ASevents in a given transcript annotation of a genome, thus providing a platform to investigate the transcriptome diversityacross genes, chromosomes, and species. Our analysis reveals that a substantial part—in human more than a quarter—ofthe observed splicing variations are ignored in common classification pipelines. We have used AStalavista to investigate andto compare the AS landscape of different reference annotation sets in human and in other metazoan species and found thatproportions of AS events change substantially depending on the annotation protocol, species-specific attributes, andcoding constraints acting on the transcripts. The AStalavista system therefore provides a general framework to conductspecific studies investigating the occurrence, impact, and regulation of AS.

"Attès los dits diputats no eran sinó procuradors...": relacions entre els braços i la diputació del general durant la celebració de les Corts Catalanes de 1599

La nostra comunicació s'emmarca en la Catalunya deIs inicis del regnat de Felip II (III de Castella). Té per objecte la complexa situació que es produeix quan, amb motiu d'una convocatoria de Corts, la Diputació del General es troba frec a frec amb els tres braços als quals està legalment subordinada. La convivència forçada d'ambdues institucions en el mateix quadre polític, ni que sigui durant lapses de temps relativament curts, esdevé cada cop més problematica a mesura que avança el segle XVI.

Report of Recommendations to the Iowa Department of Administrative Services on the Review of General and Application Controls over the HRIS and Payroll Systems, May 10, 2004 through June 4, 2004

State Audit Reports

Prescription des psychotropes au cabinet médical [Psychotropic drug prescription in general practice].

General practitioners treat patients with psychiatric disorders, for whom they have to evaluate the indication of a psychotropic medication. In addition to the patient's symptoms, the clinician has to take into account transferential and countertransferential elements linked to the prescription. Sociological factors also influence both the patient and the clinician, partly due to the western society's value of performance. Consistent with the bio-psycho-social model of disease, we recommend that the evaluation of the indication of a psychotropic medication includes the patient's symptoms, but also the psychological and sociological factors.

Report of Recommendations to Iowa State University of Science and Technology on the Review of Selected General and Application Controls over the University's Accounts Payable and Purchasing Systems, March 28 through April 28, 2005

State University Audit Report

Report of Recommendations to the Iowa Department of Workforce Development on a Review of Selected General Controls, April 18th, 2005 to May 13th, 2005

State Audit Reports

El jurament i el seu significat jurídic al principat segons els dret general de Catalunya (segles XIII-XVIII): edició de la "Forma i pràctica de celebrar els juraments i les eleccions a la ciutat de Barcelona en el segle XV"

Aquesta obra estudia els juraments pronunciats pels reis, pels oficials municipals i pels oficials reials en el municipi de Barcelona des del segle XIII fins el Decret de Nova Planta.

Appropriateness of colonoscopy in Europe (EPAGE II): presentation of methodology, general results, and analysis of complications.

BACKGROUND AND STUDY AIMS: Appropriate use of colonoscopy is a key component of quality management in gastrointestinal endoscopy. In an update of a 1998 publication, the 2008 European Panel on the Appropriateness of Gastrointestinal Endoscopy (EPAGE II) defined appropriateness criteria for various colonoscopy indications. This introductory paper therefore deals with methodology, general appropriateness, and a review of colonoscopy complications. METHODS:The RAND/UCLA Appropriateness Method was used to evaluate the appropriateness of various diagnostic colonoscopy indications, with 14 multidisciplinary experts using a scale from 1 (extremely inappropriate) to 9 (extremely appropriate). Evidence reported in a comprehensive updated literature review was used for these decisions. Consolidation of the ratings into three appropriateness categories (appropriate, uncertain, inappropriate) was based on the median and the heterogeneity of the votes. The experts then met to discuss areas of disagreement in the light of existing evidence, followed by a second rating round, with a subsequent third voting round on necessity criteria, using much more stringent criteria (i. e. colonoscopy is deemed mandatory). RESULTS: Overall, 463 indications were rated, with 55 %, 16 % and 29 % of them being judged appropriate, uncertain and inappropriate, respectively. Perforation and hemorrhage rates, as reported in 39 studies, were in general < 0.1 % and < 0.3 %, respectively CONCLUSIONS: The updated EPAGE II criteria constitute an aid to clinical decision-making but should in no way replace individual judgment. Detailed panel results are freely available on the internet (www.epage.ch) and will thus constitute a reference source of information for clinicians.